Dataset Information

Process of selecting and educating HCV-uninfected kidney waiting-list candidates for HCV-infected kidney transplantation.

ABSTRACT: Long waiting times for kidney transplant (KT) and the high risk of mortality on dialysis have prompted investigation into strategies to utilize hepatitis C virus (HCV)-infected organs to decrease discard rates of potentially viable kidneys. Due the opioid epidemic, the number of HCV-infected donors has increased significantly. With the development of direct-acting antiviral therapies for HCV infection, now more than 95% of patients who received treatment are cured. Experimental trials have used direct-acting antiviral therapy to treat HCV infection in HCV-uninfected transplant recipients of kidneys from HCV-viremic donors. To date, HCV has been eradicated in all cases. Though these strategies will potentially increase the donor pool of available kidneys, shorten waitlist times, and ultimately decrease mortality in patients waiting for KT, identifying the ideal candidates and educating them about a protocol to utilize direct-acting antiviral therapy to cure HCV after it is transmitted is essential. We present our approach to patient selection and education for a clinical trial in transplantation of HCV viremic kidneys into uninfected recipients.

SUBMITTER: Sise ME

PROVIDER: S-EPMC6733639 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

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Process of selecting and educating HCV-uninfected kidney waiting-list candidates for HCV-infected kidney transplantation.

Sise Meghan E ME Wojciechowski David D Chute Donald F DF Gustafson Jenna J Chung Raymond T RT Williams Winfred W WW Elias Nahel N

Artificial organs 20190529 9

Long waiting times for kidney transplant (KT) and the high risk of mortality on dialysis have prompted investigation into strategies to utilize hepatitis C virus (HCV)-infected organs to decrease discard rates of potentially viable kidneys. Due the opioid epidemic, the number of HCV-infected donors has increased significantly. With the development of direct-acting antiviral therapies for HCV infection, now more than 95% of patients who received treatment are cured. Experimental trials have used ...[more]

PMID: 31001828

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Project description:BACKGROUND:Patients on organ transplant waiting lists are evaluated for preexisting alloimmunity to minimize episodes of acute and chronic rejection by regularly monitoring for changes in alloimmune status. There are few studies on how alloimmunity changes over time in patients on kidney allograft waiting lists, and an apparent lack of research-based evidence supporting currently used monitoring intervals. METHODS:To investigate the dynamics of alloimmune responses directed at HLA antigens, we retrospectively evaluated data on anti-HLA antibodies measured by the single-antigen bead assay from 627 waitlisted patients who subsequently received a kidney transplant at University Hospital Zurich, Switzerland, between 2008 and 2017. Our analysis focused on a filtered dataset comprising 467 patients who had at least two assay measurements. RESULTS:Within the filtered dataset, we analyzed potential changes in mean fluorescence intensity values (reflecting bound anti-HLA antibodies) between consecutive measurements for individual patients in relation to the time interval between measurements. Using multiple approaches, we found no correlation between these two factors. However, when we stratified the dataset on the basis of documented previous immunizing events (transplant, pregnancy, or transfusion), we found significant differences in the magnitude of change in alloimmune status, especially among patients with a previous transplant versus patients without such a history. Further efforts to cluster patients according to statistical properties related to alloimmune status kinetics were unsuccessful, indicating considerable complexity in individual variability. CONCLUSIONS:Alloimmune kinetics in patients on a kidney transplant waiting list do not appear to be related to the interval between measurements, but are instead associated with alloimmunization history. This suggests that an individualized strategy for alloimmune status monitoring may be preferable to currently used intervals.

Project description:ImportanceAllocation of deceased donor kidneys is meant to follow a ranked match-run list of eligible candidates, but transplant centers with a 1-to-1 relationship with their local organ procurement organization have full discretion to decline offers for higher-priority candidates and accept them for lower-ranked candidates at their center.ObjectiveTo describe the practice and frequency of transplant centers placing deceased donor kidneys with candidates who are not the highest rank at their center according to the allocation algorithm.Design, setting, and participantsThis retrospective cohort study used 2015 to 2019 organ offer data from US transplant centers with a 1-to-1 relationship with their local organ procurement organization, following candidates for transplant events from January 2015 to December 2019. Participants were deceased kidney donors with a single match-run and at least 1 kidney transplanted locally and adult, first-time, kidney-only transplant candidates receiving at least 1 offer for a locally transplanted deceased donor kidney. Data were analyzed from March 1, 2022 to March 28, 2023.ExposureDemographic and clinical characteristics of donors and recipients.Main outcomes and measuresThe outcome of interest was kidney transplantation into the highest-priority candidate (defined as transplanted after zero declines for local candidates in the match-run) vs a lower-ranked candidate.ResultsThis study assessed 26 579 organ offers from 3136 donors (median [IQR] age, 38 [25-51] years; 2903 [62%] men) to 4668 recipients. Transplant centers skipped their highest-ranked candidate to place kidneys further down the match-run for 3169 kidneys (68%). These kidneys went to a median (IQR) of the fourth- (third- to eighth-) ranked candidate. Higher kidney donor profile index (KDPI; higher score indicates lower quality) kidneys were less likely to go to the highest-ranked candidate, with 24% of kidneys with KDPI of at least 85% going to the top-ranked candidate vs 44% of KDPI 0% to 20% kidneys. When comparing estimated posttransplant survival (EPTS) scores between the skipped candidates and the ultimate recipients, kidneys were placed with recipients with both better and worse EPTS than the skipped candidates, across all KDPI risk groups.Conclusions and relevanceIn this cohort study of local kidney allocation at isolated transplant centers, we found that centers frequently skipped their highest-priority candidates to place kidneys further down the allocation prioritization list, often citing organ quality concerns but placing kidneys with recipients with both better and worse EPTS with nearly equal frequency. This occurred with limited transparency and highlights the opportunity to improve the matching and offer algorithm to improve allocation efficiency.

Dataset Information

Process of selecting and educating HCV-uninfected kidney waiting-list candidates for HCV-infected kidney transplantation.

Publications

Process of selecting and educating HCV-uninfected kidney waiting-list candidates for HCV-infected kidney transplantation.

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